Multifunctional CD4(+) T cells correlate with active Mycobacterium tuberculosis infection

  • Caccamo N
  • Guggino G
  • Joosten S
 et al. 
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Th1 CD4(+) T cells and their derived cytokines are crucial for protection against Mycobacterium tuberculosis. Using multiparametric flow cytometry, we have evaluated the distribution of seven distinct functional states (IFN-gamma/IL-2/TNF-alpha triple expressors, IFN-gamma/IL-2, IFN-gamma/TNF-alpha or TNF-alpha/IL-2 double expressors or IFN-gamma, IL-2 or TNF-alpha single expressors) of CD4(+) T cells in individuals with latent M. tuberculosis infection (LTBI) and active tuberculosis (TB). We found that triple expressors, while detectable in 85-90%TB patients, were only present in 10-15% of LTBI subjects. On the contrary, LTBI subjects had significantly higher (12- to 15-fold) proportions of IL-2/IFN-gamma double and IFN-gamma single expressors as compared with the other CD4(+) T-cell subsets. Proportions of the other double or single CD4(+) T-cell expressors did not differ between TB and LTBI subjects. These distinct IFN-gamma, IL-2 and TNF-alpha profiles of M. tuberculosis-specific CD4(+) T cells seem to be associated with live bacterial loads, as indicated by the decrease in frequency of multifunctional T cells in TB-infected patients after completion of anti-mycobacterial therapy. Our results suggest that phenotypic and functional signatures of CD4(+) T cells may serve as immunological correlates of protection and curative host responses, and be a useful tool to monitor the efficacy of anti-mycobacterial therapy.

Author-supplied keywords

  • *Bacterial Load/immunology
  • Acute Disease
  • Acyltransferases/immunology
  • Adult
  • Antigens, Bacterial/immunology
  • Bacterial Proteins/immunology
  • CD4-Positive T-Lymphocytes/immunology/*metabolism/
  • Cell Separation
  • Chronic Disease
  • Cytokines/*secretion
  • Flow Cytometry
  • Humans
  • Lymphocyte Activation
  • Male
  • Middle Aged
  • Mycobacterium tuberculosis/*immunology/pathogenici
  • Tuberculosis, Pulmonary/diagnosis/*immunology

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  • N Caccamo

  • G Guggino

  • S A Joosten

  • G Gelsomino

  • P Di Carlo

  • L Titone

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